The project is a 5-year follow-up study of 250 depressed patients aged over 60 years, with similar proportions of early and late onset cases. Detailed psychosocial, functional, clinical, psychiatric, medical, neurologic, cognitive and neuroendocrine assessments will occur at intake and in Years 2 and 4. The principal outcome measures are severity of depressive symptoms, operationally defined remission, relapse and recurrence, functional status and dementia. We will test specific hypotheses in a multifactorial model of risk factors for adverse course of late life depression. The primary factors are psychosocial, brain structural change, and neuroendocrine dysfunctions, with medical illness and clinical features as covariates. The project will advance on past work by becoming rigorous medical and psychiatric assessments with psychosocial and psychobiologic perspectives. In a naturalistic study design we will test specific hypotheses about the salience and interactions of variables in each dimension for prognosis. Major hypotheses to be tested for risk of adverse outcome in each dimension for prognosis. Major hypotheses to be tested for risk of adverse outcome include differential course of early versus late onset cases; the moderating role of social support; cerebral vascular risk factors, including Apolipoprotein E4; brain pathology evident on MRI; and dementia related to abnormal DST status. Statistical analyses will include hierarchical linear regression models for main effects and interactions. Results of the project will clarify emerging concepts of a proposed vascular etiology depression in late life; will identify factors associated with delayed response to treatment and with relapses; will provide needed information on the timing of relapses in relation to changing social support in the elderly. Results in this clinical population will be valuable for comparison with epidemiological data. This project benefits from the resources of the Duke Mental Health Clinical Research Center for essential support.